Patent RU-2316556-C2 (RU)
Inventor: LEFTERIS KEHTERINA
IPC: C07D/
Filed: 2001-11-07
Granted: 2008-02-10
Abstract: FIELD: organic chemistry, medicine, pharmacy, biochemistry. 
     SUBSTANCE: invention relates to a method for treatment of states caused by activity of p38 kinase. Method involves administration to a patient needed in this treatment of at least one compound of the formula (I):   or its pharmaceutically acceptable salt or solvate wherein R 3  means hydrogen atom, methyl, perfluoromethyl, methoxy-group, halogen atom, cyano-group or NH 2 -group; X is chosen from -O-, -OC(=O)-, -S-, -S-, -S(=O)-, -SO 2 -, -C(=O)-, -CO 2 -, -NR 10 -, -NR 10 C(=O)-, -NR 10 C(=O)NR 11 -, -NR 10 CO 2 -, -NR 10 SO 2 -, -NR 10 SO 2 NR 11 -, -SO 2 NR 10 -, -C(=O)NR 10 , halogen atom, nitro- and cyano-group, or X is absent; Z is chosen from oxygen (O), sulfur (S), nitrogen (N) atoms, and -CR 20  being wherein Z means -CR 20  optionally substituted  bicyclic aryl or heteroaryl with R 4  or R 5 ; R 1  means hydrogen atom, -CH 3 , -OH, -OCH 3 , -SH, -SCH 3 , -OC()=O)R 21 , -S(=O)R 22 , -SO 2 NR 23 R 25 , -CO 2 R 21 , -C(=O)NR 24 R 25 , -NH 2 , -NR 24 R 25 , -NR 21 SO 2 NR 24 R 25 , -NR 21 SO 2 R 22 , -NR 24 C(=O)R 25 , -NR 24 CO 2 R 25 , -NR 21 C(=O)NR 24 R 25 , halogen atom, nitro- or cyano-group; R 2  is chosen from the following group: (a) hydrogen atom under condition that R 2  doesn't mean hydrogen atom if X means -S(=O)-, -SO 2 -, -NR 10 CO 2 - or -NR 10 SO 2 -; (b) alkyl, alkenyl and alkynyl comprising up to four R 26  groups or pentafluoroalkyl as substitutes; (c) aryl and heteroaryl comprising up to three groups R 27  as substitutes, and (d) heterocyclo-group or heteroalkyl optionally comprising keto-group (=O), up to three groups R 27  as substitutes, and/or comprising carbon-carbon bridge comprising 3-4 carbon atoms, or (e) R 2  is absent if X means halogen atom, nitro- or cyano-group; R 4  means substituted aryl, aryl comprising NOSE-alkyl, substituted heteroaryl or optionally substituted bicyclic 7-11-membered saturated or unsaturated carbocyclic or heterocyclic fragment as a substitute, and R 5  means hydrogen atom, alkyl or substituted alkyl with exception of cases when Z means O or S and then R 5  is absent, or R 4  and R 5  in common with Z form optionally substituted bicyclic 7-11-membered aryl or heteroaryl; R 6  means hydrogen atom, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo-group, substituted heterocyclo-group, -NR 7 R 8 , -OR 7  or halogen atom; R 10  and R 11  are chosen independently from the following group: hydrogen atom, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heterocyclo-group and substituted heterocyclo-group; R 7 , R 8 , R 21 , R 24  and R 25  are chosen independently from the following group: hydrogen atom, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo-group and substituted heterocyclo-group; R 20  means hydrogen, lower alkyl or substituted alkyl, or R 20  can absent if carbon atom to which is bound and in common with R 4  and R 5  represents part of bicyclic aryl or heteroaryl; R 22  means alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo-group or substituted heterocyclo-group; R 26  is chosen from the following group: halogen atom, trifluoromethyl, halogenalkoxy-group, keto (=O)-, nitro-, cyano-group, -SR 28 , -OR 28 , -NR 28 R 29 , -NR 28 SO 2 , -NR 28 SO 2 R 29 , -SO 2 R 28 , -SO 2 NR 28 R 29 , -CO 2 R 28 , -C(=O)R 28 , -C(=O)NR 28 R 29 , -OC(=O)R 28 , -C(=O)NR 28 R 29 , -NR 28 C(=O)R 29 , -NR 28 CO 2 R 29 ,=N-OH, =N-O-alkyl; aryl optionally comprising as a substitute from one to three R 27  groups; cycloalkyl optionally comprising a substituted keto-group (=O), from one to three R 27  groups, or carbon-carbon-containing bridge comprising of 3-4 carbon atoms; and heterocyclo-group comprising optionally as a substitute keto-group (=O), from one to three R 27  groups or comprising carbon-carbon bridge comprising 3-4 carbon atoms, and wherein each R 28  and R 29  is chosen independently from the following group: hydrogen atom, alkyl, alkenyl, aryl, aralkyl, (C 3 -C 7 )-cycloalkyl and (C 3 -C 7 )-heterocycle, or they can form in common (C 3 -C 7 )-heterocycle; and each R 28  and R 29 , in turn, can comprise  optionally up to two substitutes representing alkyl, alkenyl groups, halogen atoms, halogenalkyl groups, halogenalkoxy-, cyano-, nitro-, amino-, hydroxy-, alkoxy-, alkylthio-groups, phenyl, benzyl, phenyloxy- and benzyloxy-groups; and R 27  is chosen from the following group: alkyl, R 32  and (C 1 -C 4 )-alkyl comprising as substitutes from one to three R 32 groups and wherein each R 32  group is chosen independently from the following group: halogen atom, halogenalkyl, halogenalkoxy-, nitro-, cyano-groups, -SR 30 , -OR 30 , -NR 30 R 31 , -NR 30 SO 2 , -NR 30 SO 2 R 31 , -SO 2 R 30 , -SO 2 NR 30 R 31 , -CO 2 R 30 , -C(=O)R 30 , -C(=O)NR 30 R 31 , --OC(=O)R 30 , -OC(=O)NR 30 R 31 , -NR 30 C(=O)R 31 , -NR 30 CO 2 R 31  and from 3-7-membered carbocyclic or heterocyclic ring comprising optionally as a substitute alkyl, halogen atom, hydroxy-, alkoxy-group, halogenalkyl, halogenalkoxy-, nitro-, amino- or cyano-group, and wherein each R 30  and R 31  is chosen independently from the following group: hydrogen atom, alkyl, alkenyl, aryl, aralkyl, (C 3 -C 7 )-cycloalkyl, and heterocycle, or they in common can form (C 3 -C 7 )-heterocycle. Also, invention describes pyrrolotriazine compounds, a pharmaceutical composition based on thereof and a method for treatment of inflammatory diseases using above proposed compounds and pharmaceutical compositions. 
     EFFECT: valuable medicinal properties of compounds and pharmaceutical composition. 
     30 cl, 14 tbl, 152 ex